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Folate based composition for neurological and cognitive applicationsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), O-glycoside, , Oxygen Of The Saccharide Radical Bonded Directly To A Nonsaccharide Hetero Ring Or A Polycyclo Ring System Which Contains A Nonsaccharide Hetero RingFolate based composition for neurological and cognitive applications description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060148727, Folate based composition for neurological and cognitive applications. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application is a Continuation-in-Part of Ser. No. 11/002,750 filed Dec. 1, 2004 and Ser. No. 11/116,997 filed Apr. 27, 2005 and claims benefit of Provisional Application Number 60/632,681 filed Dec. 1, 2004. [0002] This application is directed to new formulations for the prevention and treatment of neurological diseases and cognitive deficiencies, i.e., Alzheimer's Disease (AD), Parkinson's Disease, ALS and other types of dimentia which comprise folate in combination with compounds chosen to address some or all of the pathways which can result in neurological deficiencies, degeneration and diseases. BACKGROUND [0003] Folic acid or salts thereof, referred to as folates, along with vitamins B.sub.6 and B.sub.12 are required in metabolic pathways involving methionine, homocysteine, cystathionine, and cysteine. The term folates as used herein is meant to include, as a minimum, folacin (USP folic acid), naturally occurring folinic acid, 5-methyl tetrahydrofolate, and tetra hydrofolate as well as salts or metabolites of these compounds. It appears that all three compounds (Folate, B.sub.6 and B.sub.12) are necessary for normal metabolism. However, these three compounds each function in a different manner. Folate, even if available at normal levels, is consumed in the metabolic process and therefore must be constantly replenished by diet or supplements. However, B6 and B12 function as co-factors. While necessary for the metabolic process to proceed, they are each regenerated in the process. Therefore, if they are present in normal amounts in serum, supplementation may not be necessary. B.sub.12 in the form of 5'-deoxyadenosylcobalamin is an essential cofactor in the enzymatic conversion of methylmalonylCoA to succinylCoA. The remethylation of homocysteine (HC) to methionine catalyzed by methionine synthase requires folate (methyltetrahydrofolate) and B.sub.12 in the form of methylcobalamin. HC is condensed with serine to form cystathionine (CT) in a reaction catalyzed by cystathionine beta.-synthase which requires B.sub.6 (pyridoxal phosphate). CT is also hydrolyzed in another B.sub.6 -dependent reaction to cysteine and alpha.-ketobutyrate. Homocysteine is a modified form of the amino acid methionine that is tightly regulated by enzymes which require folate. By impairing DNA repair mechanisms and inducing oxidative stress, homocysteine can cause the dysfunction or death of cells in the cardiovascular and nervous systems. Homocysteine appears to be present in many disease states. However, dietary folate stimulates homocysteine removal and may thereby protect cells against disease processes. [0004] The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocysteine, in the conversion of homocysteine to L-methionine. The enzyme that catalyzes the reaction is methionine synthase. Vitamin B.sub.12 is a cofactor in the reaction. This reaction, in which folate and vitamin B.sub.12 are coparticipants, is of great importance in the regulation of serum homocysteine levels. The L-methionine produced in the reaction can participate in protein synthesis and is also a major source for the synthesis of S-adenosyl-L-methionine (SAMe). The methyl group donated by 5-methyltetrahydrofolate to homocysteine in the formation of L-methionine is used by SAMe in a number of transmethylation reactions involving nucleic acids, phospholipids and proteins, as well as for the synthesis of epinephrine, melatonin, creatine and other molecules. Tetrahydrofolate is the folate product of the methionine synthase reaction. 5-Methyltetrahydrofolate is generated by conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate via the enzyme methyleneterahydrofolate reductase (MTHFR). 5,10-Methylenetetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methylenetetrahydrofolate, yields glycine. [0005] 5,10-Methylenetetrahydrofolate, in addition to its role in the metabolism of homocysteine, supplies the one-carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase. [0006] Folates are also involved in reactions leading to de novo purine nucleotide synthesis, interconversion of serine and glycine, generation and utilization of formate, the metabolism of L-histidine to L-glutamic acid, the metabolism of dimethylglycine to sarcosine and the metabolism of sarcosine to glycine. [0007] One of the natural folates, folinic acid, is used as a pharmaceutical agent. Folinic acid, also known as leucovorin, citrovorum factor and 5-formyltetrahydrofolate, is used as rescue therapy following high-dose methotrexate in the treatment of osteosarcoma. It is also used to diminish the toxicity of methotrexate. It is used in the treatment of megaloblastic anemia due to folate deficiency and in the prevention or treatment of the toxic side effects of trimetrexate and pyrimethamine. The combination of folinic acid and 5-fluorouracil has until recently been standard therapy for metastatic colorectal cancer. Folinic acid increases the affinity of flurouracil for thymidylate synthase. Folinic acid is available as a calcium salt for parenteral or oral administration. [0008] In addition to being known as pteroylglutamic acid or PGA, folic acid is known chemically as N-[4-[[(2-amino-1,4-di- hydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid. Older names for folic acid are vitamin Bg, folicin, vitamin Bc and vitamin M. Its molecular formula is C.sub.19H.sub.19N.sub.7O.sub.6 and its molecular weight is 441.40 daltons. Folic acid forms yellowish-orange crystals. The color is imparted by the pteridine ring of folic acid. Pteridine also imparts color to butterfly wings. [0009] Folate has been prescribed as a nutritional supplement for many medical conditions based on the presence of elevated homocysteine levels which occur in those conditions. Folate supplements appear to reverse the elevated homocysteine levels. However, the elevated homocysteine level may be a result of inadequate supply or excessive consumption of folate and not the cause of the disease. It is clinically beneficial in such instances to provide folate supplements as individuals with elevated homocysteine levels appear to be at increased risk for cardiovascular disease and stroke, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases as well as neural tube defects, spontaneous abortion, placental abruption, low birth weight, renal failure, rheumatoid arthritis, alcoholism, osteoporosis, neuropsychiatric disorders, non-insulin-dependent diabetes and complications of diabetes, fibromyalgia and chronic fatigue syndrome. Moderate elevations of HC might be associated with increased risk for vascular disease (Ueland et al. (1992) in Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function (Francis, Jr., ed.), Marcel Dekker, Inc., New York, pp. 183-236). However, folic acid deficiencies have also been associated with periphereal vascular disease and coronary disease in individuals with normal homocysteine levels (Bunout, D. et al "Low Serum Folate but Normal Homocysteine Levels in Patients with Atheroslerotic Vascular Disease and Matched Healthy Controls", Nutrition 2000, 16, p434-8) suggesting that folates may have a protective effect that extends beyond maintaining normal homocysteine levels. In addition, moderate hyperhomocysteinaemia has been shown to be frequently present in cases of stroke and to be independent of other stroke risk factors (Brattstrom et al. (1992) Eur. J. Clin. Invest. 22:214-221). [0010] It is not clear if the various disease states are caused by elevated homocysteine levels or the elevated homocysteine levels are caused by other factors which are the primary cause of the disease state and result in elevated levels of homocysteine. For example, it is also known that folate supplements are usefully where B.sub.12 deficiencies exist, but homocysteine levels may not be elevated. Individuals with B.sub.12 deficiency can display neurologic disorders, typically relating to underlying anemia. However, supplementing diet with only folate is not medically recommend as these folate supplements may mask the underlying B.sub.12 problem. U.S. Pat. No. 4,945,083, issued Jul. 31, 1990 to Jansen, entitled Safe Oral Folic Acid-Containing Vitamin Preparation, describes an oral vitamin preparation comprising the combination of 0.1-1.0 mg B.sub.12 and 0.1 -1.0 mg folate for the treatment or prevention of megaloblastic anemia. [0011] Normal serum folate levels in healthy individuals are 2.5-20 ng/ml, with levels less than 2.5 ng/ml indicating the possibility of clinically significant deficiency. Like B.sub.12 serum levels, however, serum folate levels are a relatively insensitive measure in that only 50-75% of patients with folate deficiency have levels less than 2.5% ng/ml, with most of the remaining 25-50% being in the 2.5-5.0 ng/ml range (Allen (1991), Cecil Textbook of Medicine, 19th Ed.). [0012] A series of patents to Allen et al, (U.S. Pat. No. 5,563,126, U.S. Pat. No. 5,795,873, U.S. Pat. No. 6,207,651, U.S. Pat. No. 6,297,224 and U.S. Pat. No. 6,528,496)) teaches the use of oral compositions or a transdermal patch delivering a combination of B.sub.12 and folate, or B.sub.12, folate and B6, in concentrations sufficient to reduce elevated homocysteine levels by treating either single or multiple deficiencies of B.sub.12, folate, and B.sub.6. The Allen non-prescription formulations include 0.3-10 mg CN-cobalamin (B.sub.12) and 0.1-0.4 mg folate or 0.3-10 mg B.sub.12, 0.1-0.4 folate, and 5-75 mg B.sub.6. The Allen prescription formulations comprise between 0.3-10 mg CN-cobalamin (B.sub.12) and 0.4-10.0 mg folate or 0.3-10 mg B.sub.12, 0.4-1.0 mg folate, and 5-75 mg B.sub.6. [0013] The standard of care for patients with Alzheimer's Disease is treatment with anticholinesterase inhibitors, currently the only approved treatment. Cholinesterase inhibitors increase the synaptic availability of the neurotransmitter acetylcholine by preventing it from breaking down. Anticholinesterase inhibitors act to stabilize progression of the disease (particularly cognitive function and overall functioning) and often delay the need for institutionalization by several months. Unfortunately, the effect of cholinesterase inhibitors is only temporary. No treatment currently exists that prevents, halts, or reverses the neurodegenerative process. SUMMARY [0014] New formulations for the prevention and treatment of neurological diseases and cognitive deficiencies and particularly Alzheimer's Disease (AD), Parkinson's Disease, ALS and other types of dimentia comprise folate in combination with compounds chosen to address some or all of the factors, pathways or mechanisms that relate to oxidative stress, glycosylation, inflammation and platelet function which can result in neurological deficiencies, degeneration and diseases. BRIEF DESCRIPTION OF THE DRAWINGS [0015] FIG. 1 is a schematic drawing of the pathophysiological processes involved in Alzheimer's disease. DESCRIPTION OF INVENTION [0016] Set forth herein is a medical food cocktail that can slow, halt or reverse the development of Alzheimer's Disease during the early stages of the disease. The cocktail is composed of nutritional ingredients that are demonstrated in the basic science and clinical medical literature to impact those specific biochemical and physiological processes thought to contribute to the onset and development of Alzheimer's Disease. These ingredients are all currently listed as Generally Accepted As Safe (GRAS) by the FDA, or are self-affirmed as GRAS ingredients, or in common use as dietary supplements. In addition, applicant has discovered that dietary supplementation with folate may be beneficial in treating certain medical conditions. In particular, compositions set forth herein, which include folates, have been found to be beneficial in preventing, reducing the severity of, or reversing various neurological diseases or cognitive disorders, including but not limited to Alzheimer's Disease, even though the individual does not appear to have a B.sub.12 deficiency or elevated homocysteine levels. These compositions may also be beneficial in preventing B.sub.12 deficiencies or elevated homocysteine levels. [0017] An objective of the invention is to provide a formulation for a medical food cocktail to be used for the prevention and treatment of Alzheimer's Disease. The cocktail will consist of standardized herbal extracts, vitamins and vitamin metabolites, and minerals that are currently listed by the FDA as generally recognized as safe (GRAS) or are self-affirmed as GRAS ingredients or are commonly used in dietary supplement. Included are ingredients that have been shown in the basic science and clinical medical literature to affect cognitive function and/or biochemical or pathophysiological processes known to be involved in Alzheimer's Disease [0018] S-adenosylmethionine (SAMe) is a substance that occurs naturally in the body. It is the combination of one (1) essential amino acid and ATP that plays a role in 35-40 biochemical reactions throughout the body. In most people, the body can make all the SAMe it needs, but some patients with depression and other psychological conditions have been found to have lower levels of the compound as well as lower levels of folate and vitamin B.sub.12. These three substances each play a part in the metabolic process of "methyl donation" or "methylation", a process in which a molecule comprised of one (1) carbon molecule and three (3) hydrogen atoms is attached to proteins and lipids. These methylation reactions are involved in the production of the neurotransmitters serotonin and dopamine in the brain and enzymes that help repair joints and the liver. There is evidence that serotonin is a factor in migraine and is involved in the so called "rebound effect", because of its vasoconstricting effect when serotonin levels are elevated and subsequent vasodilation as serotonin levels decrease. Coincidently, folate deficiency also appears to reduce brain serotonin and contribute to depression in individuals. By supplementing the diet with folate, serotonin generation and its metabolism is balanced, depression decreases and the cycling of vasodilation and vasoconstriction caused by fluctuation in serotonin is minimized. [0019] Based on a review of the literature on Alzheimer's Disease several markers and/or chemical processes have been identified that either contribute to the development of neurological or cognitive deficiencies, particularly AD, or are present in higher amounts in individuals diagnosed with AD. These are referred to herein as AD Factors. However, these factors are not limited to Alzheimer's and are found in various neurological and cognitive deficiencies. Several active compounds are identified which can be used to address these AD Factors. Polytherapy, namely the use of a cocktail or mixture of these active compounds to prevent, slow or reverse Alzheimer's Disease, Parkinsons, ALS and other types of dimentia, are set forth herein to address the multiple factors associated with the etiology or progression of the disease. Applicant has now combined several of those ingredients to reduce the dementia caused by AD, or decrease or prevent the markers or biochemical events and to be beneficial in preventing, slowing or reversing the effects of AD in human subjects. [0020] Applicant has addressed the 4 major biochemical phenomena or pathways, namely inflammation, oxidative stress, glycation/dysinsulinemia, and platelet function set forth in FIG. 1, and a key marker, homocysteine levels, that are important contributors to the development or progression of AD. Continue reading about Folate based composition for neurological and cognitive applications... 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